SHPTP2 SERVES ADAPTER PROTEIN LINKING BETWEEN JANUS KINASE 2 AND INSULIN-RECEPTOR SUBSTRATES

To investigate the role of Janus kinase family (JAK1 and JAK2) in insu lin signaling, we assessed their insulin-induced associations with oth er molecules in the cells overexpressing insulin receptors (HIRc and C HO-IR). After insulin stimulation, pp185 proteins (insulin receptor su bstrate, IRS) were co-immunoprecipitated with both kinases by alpha JA K1 aad alpha JAK2 antibodies. However. JAK2 constitutively associated with pp95 protein (IR beta). Moreover, JAK2 also constitutively bound to a protein tyrosine phosphatase containing Src 2 regions (SHPTP2), b ut JAK1 did not. In HIRc cells expressing PTPase-negative mutant SHPTP 2, no association of JAK2 with either pp185 or pp95 was detected. Thus , SHPTP2 might serve as an adapter protein linking between JAK2 and IR S. These results suggest that JAK1 and JAK2 behave differently and the y may constitute a new regulatory component in insulin signaling. (C) 1996 Academic Press, Inc.